The members of ADAMTS (A Disintegrin And Metalloproteinase with ThromboSpondin motifs) family belong to ADAM (A Disintegrin And Metalloproteinase) family of multifunctional proteins that display a significant sequence homology with snake venom metalloproteinases. The amino-terminal half of ADAMTS is similar to that of ADAM, which contains propeptide, metalloproteinase, disintegrin, and cysteine-rich domains; while the C-terminal half of ADAMTS is completely different and contains thrombospondin type I-like (TSP) motifs that are originally found in thrombospondin 1 and 2 and spacer region. At least 18 members of ADAMTS have been identified. ADAMTS-1 is the first member identified and is expressed in many embryonic tissues and in tumors. Disruption of ADAMTS-1 gene results in reduced growth, abnormalities in uteral, adrenal, and dipose tissues, and female infertility.
ADAMTS-1 cleaves aggrecan and versican in vitro, however, physiologic substrates of ADAMTS-1 remain to be identified. In addition, ADAMTS-1 is cleaved at the spacer region by matrix metalloproteinases (MMPs). The role of ADAMTS-1 in tumor growth and metastasis is not well established. ADAMTS-1 was found to display anti-angiogenic and anti-tumor activity, however, increased expression of ADAMTS-1 was correlated to the enhanced metastatic potential of pancreatic cancers, and studies have shown that ADAMTS-1 is one of the genes up-regulated in the breast cancer with elevated metastatic activity.
Thus, there is a need to clarify the biologic role of ADAMTS-1. Furthermore, there is a need to identify compounds and/or compositions that can be used to treat cancer or inhibit cell growth.